Abstract

Purpose:The pathogenesis of CTCL remains only partially understood. A number of recent studies attempted to identify novel diagnostic markers and future therapeutic targets. One group of antigens, cancer-testis (CT) antigens, normally present solely in testicular germ cells, can be ectopically expressed in a variety of cancers. Currently only a few studies attempted to investigate the expression of CT antigens in CTCL.
Experimental Design:In the present work we test the expression of CT genes in a cohort of CTCL patients, normal skin samples, skin from benign inflammatory dermatoses and in patient-derived CTCL cells. We correlate such expression with the p53 status and explore molecular mechanisms behind their ectopic expression in these cells.
Results:Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11 and GTSF1 genes are heterogeneously expressed in CTCL patients and patient-derived cell lines, while cTAGE1 was found to be robustly expressed in both. Mutated p53 status did not appear to be a requirement for the ectopic expression of CT antigens. While T cell stimulation resulted in a significant upregulation of STAT3 and JUNB expression, it did not significantly alter the expression of CT antigens. Treatment of CTCL cells in-vitro with Vorinostat or Romidepsin Histone Deacetylase inhibitors resulted in a significant dose-dependent upregulation of mRNA, but not protein. Further expression analysis demonstrated that SYCP1, cTAGE1 and GTSF1 were expressed in CTCL, but not in normal skin or benign inflammatory dermatoses.
Conclusions:A number of CT genes are ectopically expressed in CTCL patients and can be used as biomarkers or novel targets for immunotherapy.